The carcinoembryonic antigen (CEA) was first described by Gold et al in 1965; J. Exp. Med., 121, 439-462; 122, 467-487. The CEA was isolated from human colonic adenocarcinoma tissue. A radioimmunoassay for detecting CEA in patients' sera was subsequently developed by Thomson et al (1969), Proc. Nat. Acd. Sci. 64, 161. A similar diagnostic procedure has been commercialized by Roche Diagnostics Division of Hoffmann-LaRoche, Inc. Nutley, N.J. While such assay procedures are not presently recommended as a screen test to detect cancer, CEA titers can be used to monitor remission in colon and certain other types of cancer, and also for some nonmalignant inflammatory diseases. Most healthy non-smoking subjects have titer levels below 2.5 ng/ml. The elevated CEA titers that occur during disease states tend to return to levels below 2.5 ng/ml following successful therapy, but usually remain elevated when refractory disease is present.
In the CEA-ROCHE radioimmunoassay procedure, the antigen (CEA) is extracted from the plasma test sample and allowed to react with specific CEA antiserum. .sup.125 I-CEA is then added and allowed to react with the remaining CEA antiserum. The .sup.125 I-CEA bound to the antibody is separated from excess free .sup.125 I-CEA with zirconyl phosphate gel and the bound .sup.125 I-CEA determined by assay in a gamma scintillation spectrometer. The partition of .sup.125 I-CEA between bound and free fractions is a function of the amount of CEA present in the plasma. The amount of CEA present in the plasma sample is then determined from a standard inhibition curve.
The CEA for use as radio-labelled CEA in determining plasma levels has heretofore been obtained from human cancer tissue which has been surgically removed, particularly adenocarcinoma tissue of tumors originating in the digestive system. (See U.S. Pat. Nos. 3,663,684, 3,697,638 and 3,956,258, assigned to Hoffmann-LaRoche Inc.). The surgically derived cancer tissue is homogenized, and subjected to an extraction and purification procedure to obtain the CEA.
As far as is known, no process has heretofore been described for preparing a standardized CEA reference by in vitro culturing of CEA-producing cells. However, such a process would have many advantages. It would provide a stable source of CEA from well-characterized cells and thus be independent of human cancer tissue as a starting material. Moreover, it could be carried out on a production basis to provide a uniform and reproducible source of CEA. It is therefore of considerable importance that the present invention does provide such a process.